A COMBINED COMPUTATIONAL AND EXPERIMENTAL STUDY ON THE LIGAND-GATING IN CNG AND

CNG 和配体门控的综合计算和实验研究

• 批准号: 7956121
• 负责人: Lei Zhou
• 金额: $ 0.08万
• 依托单位: CARNEGIE-MELLON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-08-01 至 2010-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7956121
• 关键词: Address; Biomedical Research; Computer Retrieval of Information on Scientific Projects Database; Data; Electrostatics; Funding; Grant; High Performance Computing; Institution; Ligands; Proteins; Published Comment; Research; Research Personnel; Resources; Solvents; Source; United States National Institutes of Health; improved; research study; response

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. We appreciate the comments on the renewal application for MRAC MCB060027, A combined computational and experimental study on the ligand - gating in CNG and HCN channels, by Lei Zhou and Steven A. Siegelbaum. We found that most of the comments from both anonymous reviewers were very constructive and helpful for us to further improve the original proposal. As quoted in the Proposal Comments by Allocation Staff, one of the major technical concerns by reviewer 1 is on the weakness in the application of TI. Actually we had carried out the TI almost exactly as described by reviewer 1 (first removing electrostatic and then VDW interactions; comparing the difference between removing ligand from protein and versus removing it from bulk solvent). However, we were concerned with the file size (already 15 pages) so that we didnt present all the technical details or preliminary results in the renewal application. Here we carefully address concerns raised by both reviewers and add those technical details together with the related preliminary data. We hope that this response together with the original renewal application will satisfy these concerns and enable this proposal to be found acceptable so that we may continue the research proposed in this MRAC renewal application. Thank you for your consideration.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目和 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 我们感谢 Lei Zhou 和 Steven A. Siegelbaum 对 MRAC MCB060027 更新申请的评论，该研究是 CNG 和 HCN 通道中配体门控的综合计算和实验研究。我们发现两位匿名审稿人的大部分意见都非常有建设性，对我们进一步改进原来的提案很有帮助。正如分配人员的提案评论中所引用的，审稿人 1 的主要技术问题之一是 TI 应用中的弱点。实际上，我们几乎完全按照审稿人 1 的描述进行了 TI（首先去除静电，然后去除 VDW 相互作用；比较从蛋白质中去除配体与从本体溶剂中去除配体之间的差异）。然而，我们担心文件大小（已经有 15 页），因此我们没有在续展申请中提供所有技术细节或初步结果。在这里，我们仔细解决了两位审稿人提出的问题，并将这些技术细节与相关的初步数据一起添加。我们希望此答复与原始续展申请一起能够满足这些担忧，并使该提案能够被接受，以便我们可以继续此 MRAC 续展申请中提出的研究。感谢您的考虑。